This project is designed to investigate alternative methods of infecting Macaca nemestrina with HIV-1 to enhance pathogenesis. One method, direct inoculation of bone marrow with subsequent in vivo passage of bone marrow, was concluded early in 1998. This route of infection did not appear to enhance pathogenesis in this species. Another project was the inoculation of neonate macaques (<1 week of age), whose immature immune systems would be less likely to clear or control the infection. After the first group of infants was infected by inoculation via intravenous and intrarectal administration, a serial in vivo passage was instituted to increase the pathogenicity. To date, three pairs of infants have been inoculated as part of this in vivo passage. After infection was confirmed in the first pair, peripheral lymph nodes and blood were used to generate a virus stock for passage. This virus stock was then inoculated into the next pair of infant macaques, by intravenous an d in trarectal inoculation. The lymph node and blood harvest for virus stock was again repeated and passaged into the third pair of infants. To date, the level of viremia in the infants has been increasing with each passage, and is becoming more persistent. At the same time, all the infants undergo a series of developmental and behavioral tests, as do normal infant macaques at the Infant Primate Research Laboratory. The results of these tests will be compared with the normal standards, as developed by the IPRL, to determine subtle motor and learning delays that may be attributed to infection with HIV-1. FUNDING NIH grant RR00166.